Biomedical subjects

H Kawashima

Publications and source records attributed to H Kawashima.

At least 181 records · Page 10Linked to original sources

PubMed1996

Circadian variations of blood pressure in patients with sequelae of carbon monoxide poisoning.

It has been shown that carbon monoxide poisoning causes necrosis of the globus pallidum and the cerebral cortex, and a diffuse demyelination of the cerebral subcortical white matter, resulting in the impairment of the higher brain functions manifested as memory disturbances, apraxia, and agnosia. The purpose of the present study was to determine the effects of the lesions in the brain caused by carbon monoxide poisoning on the circadian changes in blood pressure and pulse rate. We measured the ambulatory blood pressure in 15 male patients with the sequelae of acute carbon monoxide poisoning and 16 age- and sex-matched controls. Using either brain computed tomography or brain magnetic resonance imaging, we determined that seven patients had lesions in the globus pallidum bilaterally, four had lesions in the parietotemporooccipital lobe bilaterally, and five had multiple deep white matter lesions. Circadian variations of blood pressure and pulse rate did not show any significant differences in either group. The average 24-h blood pressures were 120.8 +/- 2.2 (systolic)/74.1 +/- 1.5 mm Hg (diastolic) in the patients and 117.4 +/- 2.7/74.5 +/- 2.1 mm Hg in the controls. The daytime (6:00 to 21:00) and nighttime (21:00 to 6:00) blood pressures were 127.3 +/- 2.3/78.0 +/- 1.5 mm Hg and 109.7 +/- 2.4/67.4 +/- 1.7 mm Hg in the patients, and 121.6 +/- 2.9/77.5 +/- 2.2 mm Hg and 110.0 +/- 2.7/69.3 +/- 1.8 mm Hg in the controls, respectively. Furthermore, there were no differences in cardiovascular and plasma catecholamine responses induced by either a head-up tilt or a cold pressor test between the two groups. It is concluded that diffuse or multiple lesions in bilateral cerebral hemispheres caused by carbon monoxide poisoning per se do not affect the circadian changes in blood pressure and pulse rate observed in normotensive subjects.

Aged↗

PubMed1996

Cancer-associated retinopathy in a patient with endometrial cancer.

PURPOSE: We studied a case of unusual retinopathy in a 60-year-old woman. METHOD: The patient developed bilateral retinopathy with iridocyclitis and vitreitis. Corticosteroid therapy could not prevent deterioration of visual acuity and field. The electroretinogram became nonrecordable, and fluorescein angiogram exhibited retinal pigment epithelium window defects, fluorescein stainings to the vascular walls, and narrowed arterioles. RESULTS: The patient underwent hysterectomy and lymphadenectomy for endometrial cancer in the corporis uteri. She was found to possess antibodies against retinal 34-kd protein, leading to a diagnosis of cancer-associated retinopathy. CONCLUSION: Cancer-associated retinopathy may occur in patients with endometrial cancer of the corporis uteri.

Antibodies, Neoplasm↗

PubMed1996

[1-11C]octanoate as a potential PET tracer for studying glial functions: PET evaluation in rats and cats.

To evaluate the ability of [1-11C]octanoate as a PET tracer for imaging the brain, we examined its distribution in the brain and surrounding tissues in rats and cats with PET. In rats, owing to the accumulated radioactivity in the harderian glands, clear brain images were not obtained at rostral levels. In cats, the brain was imaged clearly at every level of the coronal brain slices, suggesting the potential of [1-11C]octanoate for imaging the brain.

Animals↗

PubMed1996

Substrate specificity of recombinant osteoclast-specific cathepsin K from rabbits.

A cDNA clone encoding the rabbit cysteine proteinase cathepsin K, which is predominantly expressed in osteoclasts and is closely related to cathepsins L (EC 3.4.22.15) and S (EC 3.4.22.27) [Tezuka K., Tezuka Y., Maejima A., Sato T., Nemoto K., Kamioka H., Hakeda Y., Kumegawa M., J. Biol. Chem., 269, 1106 (1994)], was expressed at high levels in Escherichia coli in a T7 expression system. The insoluble recombinant enzyme was solubilized in urea and refolded at an alkaline pH. Cathepsin K (37-kDa) was purified by gel filtration and its enzymatic characteristics were determined. The enzymatic activity of cathepsin K was strongly inhibited by cysteine proteinase inhibitors and its optimal pH was pH 5.5. Synthetic substrate benzyloxycarbonyl-Phe-Arg-7-(4-methyl)coumaryl-amide, which is hydrolyzed by cathepsins L and S, was also cleaved by cathepsin K. On the other hand, benzyloxycarbonyl-Gly-Pro-Arg-7-(4-methyl)coumaryl-amide was the most suitable substrate for cathepsin K, but was hardly hydrolyzed by cathepsin L. The substrate specificity of cathepsin K, as determined using various chemogenic substrates, showed different characteristics from cathepsins L and S.

Amino Acid Sequence↗

PubMed1996

Inhibition of rat liver microsomal desaturases by curcumin and related compounds.

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) inhibited noncompetitively rat liver microsomal delta 5 desaturase (Ki = 36 microM) and delta 6 desaturase (Ki = 28 microM). Although curcumin has a symmetrical structure with a methylene group as the center, only half the structure is essential for the desaturase inhibition. The structure necessary for the inhibition is similar to that of alkyl gallate (H. Kawashima et al., Biochim. Biophys. Acta, in press), i.e., a 3-hydroxy group of the aromatic ring is essential for the inhibition and a free carboxyl group at the end opposite to the aromatic ring interferes with the inhibitory effect. The following structural features of curcumin are necessary for the desaturase inhibition: (i) the aromatic ring conjugated with the double bond between the 1 and 2 (or 6 and 7) positions; (ii) both 4-hydroxy and 3-methoxy groups (for both desaturase inhibitions); and (iii) only a 4-hydroxy group (for delta 6 desaturase inhibition).

Animals↗

PubMed1996

Nicardipine and nifedipine inhibit fatty acid desaturases in rat liver microsomes.

Nicardipine and nifedipine, Ca channel blockers, inhibited rat liver microsomal desaturases, though verapamil, methoxyverapamil, cinnarizine, flunarizine, and diltiazem did not. However, nicardipine and nefidipine apparently did not inhibit the fungal desaturation in Mortierella alpina 1S-4. Nicardipine inhibited rat liver microsomal delta 5 desaturase specifically (50% inhibitory concentration. 170 microM), and nifedipine inhibited delta 6 desaturase specifically (78 microM). The inhibition by nicardipine and nifedipine is uncompetitive, the Ki values for delta 5 and delta 6 desaturases being 62 and 44 microM, respectively.

Animals↗

PubMed1996

[A 10-year-old girl with anticardiolipin antibody, who showed bleeding tendency].

We described a 10-year-old girl with SLE complicated with anticardiolipin antibody, who showed bleeding tendency since infant. Her platelet was 6 x 10(3)/microliter. The APTT was remarkably prolonged. The platelet count was normalized after steroid treatment. A false positive Venereal Disease Research Laboratory (VDRL) test, lupus anticoagulants and anticardiolipin antibodies (IgG and IgM) were positive. Her symptoms and the laboratory data fulfilled the criteria of antiphospholipid syndrome. Renal biopsy was performed because of proteinuria, hematuria and the positive of anti-nuclear antibody. The pathology of kidney showed that of lupus nephritis (diffuse membranous glomerulonephritis), and she was diagnosed SLE. She showed no laboratory findings of hyperfibrinolysis and no symptoms of thrombosis under the steroid treatment for 3 years.

Antibodies, Anticardiolipin↗

PubMed1996

[Fat suppressed dynamic MR imaging of breast cancer: radiologic-pathologic correlation].

Fat-suppressed spoiled gradient-echo imaging was performed on 35 preoperative patients with breast cancer. Whole breast images using coronal sections were obtained immediately after bolus injection of Gd-DTPA. The images were reviewed regarding detectability of the lesion, irregularity of its margin, homogeneity of contrast enhancement and detectability of intraductal spread. The results were correlated with the histopathologic findings. All breast tumors were identified on dynamic MRI. The existence of mastopathy and lactating change obscured the lesion border. Scirrhous carcinomas exhibited speculation. They showed inhomogeneous enhancement, and time-intensity curves variety might be due to different amounts of fibro-connective tissue within the tumor. Solid-tubular and papillotubular carcinomas showed well-defined borders. They exhibited septum and rim enhancement corresponding to fibrous stroma. The peak of their time-intensity curves was within 3 minutes. Fifty-five percent of cases of intraductal spread were visualized on dynamic MRI. Those lesions had large numbers of cancer cells in the ducts and also showed periductal inflammation. The histologic type of breast cancer was well reflected in the enhancement pattern. The ability of dynamic MRI to detect all intraductal components of breast cancer was limited.

Adenocarcinoma, Scirrhous↗

PubMed1995

cDNA cloning of three new forms of rat brain cytochrome P450 belonging to the CYP4F subfamily.

Three cDNA clones, designated 4f-8, 4f-34 and 4f-41, coding for three new forms of cytochrome P450 belonging to the CYP4F subfamily were isolated from an untreated rat brain cDNA library. cDNA 4f-8, 4f-34 and 4f-41 coded for proteins of 522, 526 and 537 amino acids, respectively, and their amino acid sequence similarity to CYP4F1 ranged from 71 to 80%. These new P450s were thus named CYP4F4, 4F5 and 4F6, respectively. Northern blot analysis revealed that the expression levels of these forms of P450 in the brain were somewhat low and that similar forms of subfamily 4F P450 were expressed in liver and kidney at a relatively high level compared with brain. No CYP4A expression was detected by Northern blot analysis in untreated rat brain mRNA. All three clones were in vitro-translatable using a reticulocyte lysate system. These results show that multiple forms of subfamily 4F P450 exist in the brain and that the subfamily 4F P450 may be one of the major forms of P450 in the brain.

Amino Acid Sequence↗

PubMed1995

Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase.

The phosphorylation of the human estrogen receptor (ER) serine residue at position 118 is required for full activity of the ER activation function 1 (AF-1). This Ser118 is phosphorylated by mitogen-activated protein kinase (MAPK) in vitro and in cells treated with epidermal growth factor (EGF) and insulin-like growth factor (IGF) in vivo. Overexpression of MAPK kinase (MAPKK) or of the guanine nucleotide binding protein Ras, both of which activate MAPK, enhanced estrogen-induced and antiestrogen (tamoxifen)-induced transcriptional activity of wild-type ER, but not that of a mutant ER with an alanine in place of Ser118. Thus, the activity of the amino-terminal AF-1 of the ER is modulated by the phosphorylation of Ser118 through the Ras-MAPK cascade of the growth factor signaling pathways.

Amino Acid Sequence↗

PubMed1995

Cloning and expression of PCPTP1 encoding protein tyrosine phosphatase.

A novel cDNA encoding PTP (protein tyrosine phosphatase) was cloned from PC12h cells and designated as PCPTP1 (gene encoding PC12 protein Tyr phosphatase). The longest open reading frame (ORF) of this clone encodes a 656-amino-acid (aa) protein with a single PTP catalytic domain. Western blot analysis using a polyclonal Ab (antibody) raised against the cytoplasmic region of PCPTP1 detected two products, a major 65-kDa and minor 42-kDa protein, designated PCPTP1-MFI and PCPTP1-MVQ, respectively, in PC12h cells. These two proteins correspond to the products translated from the second and fifth methionine of PCPTP1, respectively. The bacterially expressed GST::PCPTP1-MVQ fusion protein had phosphatase activity with pNPP (p-nitrophenyl phosphate) as a substrate. Alignment of the aa sequence of PCPTP1-MVQ with those of other PTP showed the highest similarity to STEP and LC-PTP/HePTP, with 54 and 51% identity, respectively. Northern blot analysis showed only one 3.9-kb transcript in PC12h cells, indicating that PCPTP1 corresponds to this 3.9-kb transcript. The 3.9-kb PCPTP1 mRNA was detected in the brain and adrenal gland, but not in other non-neuronal tissues in adult rats. Two other transcripts of 3.3 and 1.7 kb were also detected in brain. NGF (nerve growth factor) and glucocorticoid are known to bimodally regulate the cell fate decision of sympathoadrenal precursors like PC12 cells, with NGF promoting the neuronal phenotype and glucocorticoid promoting the chromaffin phenotype. Still, both agents decreased the level of PCPTP1 mRNA in PC12h cells. Therefore, it is likely that the decrease in the level of PCPTP1 mRNA might be associated or correlated with cell differentiation in PC12h cells.

Amino Acid Sequence↗

PubMed1995

Preparation of 13C-labeled polyunsaturated fatty acids by an arachidonic acid-producing fungus Mortierella alpina 1S-4.

Three types of 13C-labeled polyunsaturated fatty acids (PUFAs) were produced in mycelia of an arachidonic acid-producing fungus, Mortierella alpina 1S-4, when grown with 13C-labeled glucose or fatty acid methyl esters. We analyzed them by negative-ion fastatom bombardment mass spectrometry. (i) PUFA in mycelia grown with [1-(13)C]glucose or [2-(13)C]glucose was a mixture of molecules containing zero to six labeled carbons. The content of 13C in the total carbon atoms of PUFA, such as arachidonic (20:4 omega 6), dihomo-gamma-linolenic (20:3 omega 6), gamma-linolenic (18:3 omega 6), and linoleic (18:2 omega 6) acids, in the mycelia grown with [1-(13)C]-glucose or [2-(13)C]glucose was about 11 or 15%, respectively. More than 80% of these PUFA had more than one 13C atom. (ii) When the fungus was grown with [U-13C]glucose, the content of PUFA molecules, all carbons of which were 13C-labeled, was about 20%. The percentage of 13C in PUFA from [U-13C]glucose was 78-83%, over 98% of which had more than one 13C atom. The 13C atoms in the labeled fatty acids formed from 13C-labeled glucose were thought to be distributed at random by a two carbon-unit. (iii) The 13C atom of PUFA in mycelia grown with 1-(13)C-labeled fatty acid methyl esters was highly localized. More than half of the 20:4 omega 6 molecules had only one 13C atom at C-3, C-5, or C-7 when the fungus was grown with methyl [1-13c]stearate, methyl [1-(13)C]palmitate, or methyl [1-(13)C]-myristate, respectively.

Arachidonic Acid↗

PubMed1995

Molecular cloning and characterization of rat V1b vasopressin receptor: evidence for its expression in extra-pituitary tissues.

Arginine vasopressin (AVP) modulates the secretion of ACTH through vasopressin receptor subtype V1b in the pituitary. We recently cloned human V1b, but several inconsistencies were found between the characteristics of this cloned receptor and those of rat pituitary membrane shown by previous workers. To clarify this issue, we report here the molecular cloning and functional expression of the cDNA encoding V1b in rat pituitary. This receptor encodes 425 amino acid protein having the highest identity with the human V1b (81%). Expression of this receptor in COS-1 cells showed pharmacological characteristics of V1b consistent with those of rat pituitary membrane. Northern blot and RT-PCR analyses revealed that mRNA of this receptor was expressed not only in anterior pituitary, but also in other tissues. This finding raises the possibility that V1b may play a role in regulating cell functions of these tissues.

Amino Acid Sequence↗

PubMed1995

Purification and characterization of two forms of cytochrome b5 from an arachidonic acid-producing fungus, Mortierella hygrophila.

Two forms of cytochrome b5 have been purified from the microsomes of an arachidonic acid-producing fungus, Mortierella hygrophila IFO 5941, after detergent solubilization. They have monomeric molecular masses of about 16 kDa and 19 kDa. Their absorption spectra are similar to those of mammalian cytochrome b5s. Their amino acid compositions show some similarity to those of mammalian cytochrome b5s, but the contents of some amino acids (glycine, alanine, aspartic acid + asparagine, glutamic acid + glutamine, arginine, proline, histidine, leucine and lysine) are unique to the cytochrome b5s of M. hygrophila. Some of their internal peptide sequences also show close homology with those of some mammals (approx. 65 to 67%), while some others show no or little homology. The addition of various acyl-CoAs to NADH-reduced microsomes caused an abrupt shiftdown of the steady state reduction level of cytochrome b5. This indicates the increased utilization of electrons for the desaturation process and may suggest that the cytochrome b5s of this fungus actually take part in its microsomal desaturation system for polyunsaturated fatty acid biosynthesis as electron carriers.

Amino Acid Sequence↗

PubMed1995

Pathologic Assessment of Surgical Margins on Frozen and Permanent Sections in Breast Conserving Surgery.

The diagnostic value of frozen section was evaluated in the histologic assessment of surgical margins obtained by wide excision of breast tumors. There were 87 patients with unilateral breast cancer, and 5 with bilateral breast cancers. The periphery of the excised breast tissue was peeled like an orange and histologically examined by frozen and permanent section. If either in situ or infiltrating microscopic tumor was found at the margin, it was considered positive. Using frozen sections, the margin was judged histologically positive or suspicious in 30 tumors (31%) and negative in 67(69%) tumors. Positive surgical margins were histologically confirmed by permanent section in 20(67%) of the 30 tumors diagnosed as positive or suspicious on frozen section. Another 10 tumors had negative margins. In 4 tumors, however, while the initial or re-excised margin was negative on frozen section, the margins were positive by permanent section. These surgical margins were positive due exclusively to the presence of ductal carcinoma in situ (DCIS). Evaluation of surgical margins in breast cancer by frozen section, thus exhibited a diagnostic accuracy of 86&prtcnt;, a sensitivity of 83%, and a specificity of 86%. It is concluded that frozen sections are useful in the determination of involvement of surgical margins after the wide excision of breast cancer. It must be pointed out that frozen sections will ofter overestimate involvement of the surgical margins.

Journal Article↗

PubMed1995

cDNA cloning of a novel rat brain cytochrome P450 belonging to the CYP2D subfamily.

Two cDNA clones designated 2d-29 and 2d-35 encoding a novel P450 belonging to the P450 2D subfamily were isolated from control and imipramine-treated rat brain libraries, respectively. cDNA 2d-29 and 2d-35 contained 1786 and 2754 bp nucleotides each. Although their 5'- and 3'-untranslated sequences were different from each other, their open reading frames were identical, encoding a protein which had 5 substitutions of amino acids in the C-terminal region compared with P450 2D4. Northern blot analysis showed that the expression levels of 2d-29 and 2d-35 in the brain were lower than that of P450 2D4 in the liver. However, it is noteworthy that the expression of 2d-35 was not detected in the liver but in the brain. These results suggest that a novel P450 is expressed in the brain under different regulation.

Amino Acid Sequence↗

PubMed1995

Effects of the bisphosphonate YM175 on bone mineral density, strength, structure, and turnover in ovariectomized beagles on concomitant dietary calcium restriction.

We evaluated the effect of YM175 on bone in ovariectomized beagles fed a calcium-restricted diet for 18 months. Groups 1 (n = 6) and 2 (n = 6) underwent sham operation, and groups 3-6 were ovariectomized at the age of 21 months. Group 1 was fed standard dog chow (calcium: 1.4%), and groups 2-6 were given a low calcium diet (0.14%). Groups 3 (n = 7), 4 (n = 7), 5 (n = 7), and 6 (n = 7) were given YM175 orally at doses of 0, 0.01, 0.1, and 1.0 mg/kg/day, respectively. At the end of the experimental period, bone mineral density values measured in the lumbar (L2) vertebra, the femoral neck, and the midfemur, were reduced in groups 2 and 3. Bone strength, measured by compression tests on L2 body and L3 cancellous core specimens and by bending tests on the femoral neck, also decreased. YM175 treatment dose-dependently increased the values of these parameters. However, the reduction in torsional stiffness in the midfemur was not completely prevented. In the L4 body, trabecular thickness decreased in group 2 and trabecular separation increased in group 3. YM175 treatment prevented these changes, and the values in group 6 were maintained at the same levels as those in group 1. Bone formation rates were increased in groups 2 and 3. YM175 treatment decreased these indices, but the reduction was incomplete even with the highest dose (group 6). These results demonstrate that, in our model, YM175 maintained the mass, structure, and mechanical properties of cancellous bone. Increased bone turnover was not completely prevented by the doses employed, but the balance between net resorption and formation in one remodeling cycle would have been equilibrated by YM175.

Administration, Oral↗

PubMed1995

Oncologic and cosmetic outcome in patients with breast cancer treated with wide excision, transposition of adipose tissue with latissimus dorsi muscle, and axillary dissection followed by radiotherapy.

We evaluated the oncologic and cosmetic outcome in patients with breast cancer treated with wide excision, transposition of adipose tissue with latissimus dorsi muscle (LDM), and axillary dissection followed by radiotherapy. In this study, a wide excision of breast tissue was performed to obtain tumor-free margins. The subsequent breast deformity was not corrected in six patients in the early phase of the study (Group 1), and in 16 patients in the late phase (Group 2) in which the breast deformity was not remarkable at the time of operation. Breast deformity was corrected by transposing adipose tissue with LDM on a vascular pedicle in the remaining 51 patients (Group 3). Five year survival was 100%. Two patients developed distant metastases. None were found to have local recurrence. Fifty percent of the Group 1 patients, 69% of the Group 2 patients, and 67% of the Group 3 patients had an excellent or good cosmetic result. However, when the cosmetic results were evaluated in patients who underwent transposition and had small breasts, the results were excellent or good in 76%, compared to 38% in the patients who had reconstructions who had large breasts. The difference was statistically significant (p = 0.0309). Therefore, it was confirmed that wide excision and axillary dissection followed by breast radiation could provide adequate local control, but frequently resulted in breast deformity. However, transposition of adipose tissue may be useful to correct the breast deformity, especially in women with small breasts.

Adipose Tissue↗